RESUMO
The elimination pharmacokinetics of tobramycin sulfate was studied in 25 newborn infants of birth weight 0.7 to 4.7 kg during 31 treatment episodes. The peak serum concentrations after a 2.5 mg/kg dose were usually within the therapeutic range of 5 to 10 micrograms/ml; however, the serum predose trough values were elevated above the theoretical safe limit of 2 micrograms/ml. Because of the prolonged serum elimination half-lives, a calculated extended dosage interval, sometimes greater than 24 hours, was necessary to obtain a predose trough of less than or equal to 2 micrograms/ml. The serum elimination half-lives inversely correlated with gestational age, extrauterine age, birth weight, and creatinine clearance. The very low ratio of tobramycin renal clearance to creatinine renal clearance was virtually constant and indicated a probable tubular reabsorption of tobramycin. A general dosage schedule based on birth weight was derived from the data. An alternative formula was derived to enable prediction of the tobramycin elimination half-life based on a combination of birth weight, gestational age, and extrauterine age for an infant younger than 7 days of age.
Assuntos
Antibacterianos/metabolismo , Infecções Bacterianas/tratamento farmacológico , Recém-Nascido de Baixo Peso , Doenças do Prematuro/tratamento farmacológico , Tobramicina/metabolismo , Esquema de Medicação , Meia-Vida , Humanos , Recém-Nascido , Rim/metabolismo , Cinética , Tobramicina/uso terapêuticoRESUMO
Limited pharmacokinetic data are available concerning the disposition of indomethacin in preterm infants. Since oral absorption of the drug may be poor or incomplete, the current report provides pharmacokinetic data on 37 premature infants who received indomethacin intravenously. Each of these infants had a hemodynamically significant patent ductus arteriosus. Findings included variable serum indomethacin concentrations from four to 12 hours after a single dose of 0.2 mg/kg. Female preterm infants generally had lower serum drug values at 12 hours and beyond when compared to males. An extrauterine age dependence was found of serum indomethacin levels. Total body clearance, serum half lives and volumes of distribution also bore a direct relationship to extrauterine age. Thus, when indomethacin is administered shortly after birth, one may anticipate a longer duration of action after a single dose and a relatively greater risk of accumulation of the drug when more than one dose is required for treating a duct al patency.